FDA: Risks of new asthma drugs vary

[December 06, 2008]  WASHINGTON (AP) -- The blockbuster asthma drug Advair does not appear to have an increased risk of serious respiratory complications seen with similar new medicines, federal health officials said Friday.

But a less widely used medication, Serevent, had a significantly higher rate of complications when compared to older treatments, the Food and Drug Administration said. Both drugs are made by the same company, GlaxoSmithKline. FDA safety reviewers are recommending that Serevent no longer be approved for treating asthma.

The FDA is concerned about asthma drugs known as LABAs, which already carry warnings. The long-acting medications relax tight muscles around stressed airways and free patients from the need to take a puff from their inhaler every few hours. For many asthma sufferers, that means they can sleep through the night.

But LABAs, for reasons that are still being debated, can increase risks of death and respiratory complications in some patients. The risk may be lower when a LABA is used together with a steroid to treat underlying inflammation deep inside the airways. Current medical guidelines suggest using both kinds of drugs together for patients with chronic asthma who are not responding well to other treatments.

Advair combines both medicines in one inhaler. But Serevent is a LABA-only product.

Asthma is a chronic respiratory illness that leaves patients short of breath, wheezing, and can sometimes send them to the emergency room because of difficulty breathing. Some 22 million people in the United States suffer from asthma, and children account for nearly one out of every three patients. Nearly 3,600 people still die from asthma in this country each year, although symptoms can be controlled with medication to prevent the most serious complications.

The FDA analyzed reams of clinical data on four drugs: Advair, Foradil, Serevent and Symbicort. All four already carry the FDA's strongest warning, but the findings could lead to more specific instructions for patients and greater restrictions, or withdrawal, of some of the medications. The agency has called a special two-day meeting of outside advisers next week to discuss the data and make recommendations.

A review team from the FDA's safety office unanimously recommended that Serevent and Foradil, the two LABA-only drugs, no longer be approved for treating asthma. Safety reviewers also recommended that none of the drugs be used to treat children, because clinical data indicates they are at greater risk of developing respiratory complications with LABAs.

The FDA's outside scientific advisers will vote on whether the drugs should remain on the market for asthma, and whether their use in children should be curbed.

GlaxoSmithKline said the analysis underscored its confidence in Advair, its best-selling medication, with U.S. sales of $2.9 billion in the first nine months of this year. But a spokeswoman declined to comment on a possible withdrawal of Serevent, which had U.S. sales of $97 million in the same period. About 3.9 million U.S. patients now use Advair, and an estimated 162,000 take Serevent.

"We don't believe LABAs are inherently unsafe or toxic," said Dr. Kate Knobil, a Glaxo executive who oversees asthma drugs. "What we do know is that poorly treated asthma is what is causing the increase in asthma-related complications. If you don't also treat the inflammation inside the airways (with a steroid) patients are going to have worse outcomes."

For patients, the advantage of using LABAs is that they have to take medications less often, usually once every 12 hours. But some doctors believe that the convenience and relief LABAs offer can mask problems that develop slowly. Deep inside airways in the lungs, passages can become inflamed or clogged with mucus unless patients are also taking a steroid. At some point, that congestion can become acute, leaving patients to gasp for air.

The FDA analysis compared patients taking a LABA drug to those using steroids alone to control their asthma. It compared the number of deaths, hospitalizations and cases where a patient had to have a breathing tube inserted. The agency analyzed findings from 110 clinical trials involving nearly 61,000 patients.

The analysis found 20 asthma-related deaths, of which 16 were in patients taking a LABA drug. All of those deaths were among patients treated with Serevent.

In terms of overall risk of complications, Foradil, Serevent and Symbicort had a higher rate when compared to treatment with steroids. But the FDA said the difference was statistically significant only in the case of Serevent.

[Associated Press; By RICARDO ALONSO-ZALDIVAR]

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